Platelets aggregate with neutrophils and promote skin pathology in psoriasis

Franziska Herster, Zsofia Bittner, Marius Cosmin Codrea, Nathan Archer, Martin Heister, Markus W. Löffler, Simon Heumos, Joanna Wegner, Ramona Businger, Michael Schindler, David Stegner, Knut Schäkel, Stephan Grabbe, Kamran Ghoreschi, Lloyd S Miller, Alexander N.R. Weber

Research output: Contribution to journalArticle

Abstract

Psoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes, but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well-defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental in vivo mouse model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease incidence directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in mice in vivo ameliorated disease severity significantly, indicating that both PMNs and platelets may be relevant for psoriasis pathology and disease severity.

Original languageEnglish (US)
Article numberArticle 1867
JournalFrontiers in immunology
Volume10
Issue numberAUG
DOIs
StatePublished - Jan 1 2019

Keywords

  • Imiquimod
  • Neutrophil
  • Platelet
  • Platelet-neutrophil complexes (PNCs)
  • Psoriasis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Herster, F., Bittner, Z., Codrea, M. C., Archer, N., Heister, M., Löffler, M. W., Heumos, S., Wegner, J., Businger, R., Schindler, M., Stegner, D., Schäkel, K., Grabbe, S., Ghoreschi, K., Miller, L. S., & Weber, A. N. R. (2019). Platelets aggregate with neutrophils and promote skin pathology in psoriasis. Frontiers in immunology, 10(AUG), [Article 1867]. https://doi.org/10.3389/fimmu.2019.01867